Diagnosis of Inherited Defects of Cholesterol Biosynthesis

Abstract

Cholesterol is synthesized endogenously in a complicated pathway, which falls apart in a non-sterol or isoprenoid part and a sterol part, starting with lanosterol. Analysis of plasma or tissue / cellular sterols by gas chromatography of underivatized sterols and / or gas chromatography / mass spectrometry of trimethylsilylated sterols may be used for the diagnosis of the known defects of cholesterol biosynthesis such as 3β-hydroxysterol-∆7–reductase deficiency (Smith-Lemli-Opitz syndrome), 3β-hydroxysterol-∆24–reductase deficiency (desmosterolosis), 3β-hydroxysterol-∆5–desaturase deficiency (lathosterolosis), 3β-hydroxysterol-∆14reductase deficiency (HEM skeletal dysplasia), and 3β-hydroxysterol-∆8-∆7–isomerase deficiency (Conradi Hunermann syndrome). In addition, cerebrotendinous xanthomatosis and sitosterolemia may be picked up using this technique. The only inborn error of the isoprenoid part of the pathway, i.e. mevalonate kinase deficiency, requires the analysis of organic acids.